Sequencing CAR T-Cell Therapy and Bispecifics to Preserve T-Cell Fitness

With both CAR T-cell therapy and bispecific antibodies now available in early relapse, Adam D. Cohen, MD, director of Myeloma Immunotherapy and professor of medicine at the Hospital of the University of Pennsylvania, asked how clinicians should decide which modality comes first. Matthew J. Frigault, MD, clinical director of the Cellular Immunotherapy Program at Mass General Brigham Cancer Institute, said the guiding principle is to treat the patient in front of you. In the case of rapidly progressive or symptomatic disease, for example, reaching for an available bispecific antibody to gain control makes sense.

Frigault noted that the NCCN guidelines suggest avoiding BCMA-targeted therapy before CAR T-cell therapy when possible, and that ASCO guidelines prefer ciltacabtagene autoleucel (cilta-cel; Carvykti) for BCMA-naive patients who are eligible for CAR T-cell therapy.1,2 Regardless, with durable results for teclistamab-cqyv (Tecvayli) plus daratumumab (Darzalex) in the phase 3 MajesTEC-3 trial (NCT05083169), he said there is no single wrong answer.3

Before apheresis, Frigault said he recommends avoiding bendamustine (Treanda), other alkylating agents, and prolonged bispecific exposure because the quality of the collected cells affects the final product. Retrospective series suggest inferior outcomes when patients receive CAR T-cell therapy within about 6 months of prior BCMA-targeted therapy. After collection, talquetamab-tgvs (Talvey) can serve as bridging therapy to debulk disease before BCMA-directed CAR T-cell consolidation.

Cohen urged community oncologists to refer early, even at first relapse, without necessarily holding therapy. A patient starting daratumumab, carfilzomib (Kyprolis), and dexamethasone (DKd), for example, could later consolidate that response with CAR T-cell therapy. His advice was to refer early and often so patients are already in the system when they need it.